Anemoside B4 mitigates endoplasmic reticulum stress-induced apoptosis post cerebral ischemia/reperfusion injury in rats

Document Type : Original Article

Authors

1 Department of Pathology, Chongqing Three Gorges Medical College, Wanzhou, China

2 Chongqing Three Gorges Medical College, Wanzhou, China

3 Medical college, Jiujiang University, Jiujiang, Jiangxi Province , China

10.22038/ijbms.2025.85441.18475

Abstract

Objective(s): Anemoside B4 (AB4) exhibits neuroprotective effects on cerebral ischemia/reperfusion injury (CIRI), and endoplasmic reticulum stress (ERS) plays a crucial role in the process of CIRI. Nevertheless, it remains unknown whether AB4 acts on CIRI via ERS. This study is designed to determine whether AB4 mitigates CIRI by suppressing ERS-induced neuronal apoptosis.
Materials and Methods: One hundred thirty-five male SD rats (260–290 g) were randomly assigned to five groups, with 20 rats in each group: ① Sham. ② Middle Cerebral Artery Occlusion (MCAO/R). ③AB4-L: Prior to MCAO, rats were subjected to continuous intraperitoneal injection of 1.25 mg/kg of AB4.④AB4-M: Rats were administered a continuous intraperitoneal injection of 2.5 mg/kg of AB4 prior to undergoing MCAO.⑤AB4-H: Rats were continuously intraperitoneally injected with 5 mg/kg of AB4 before MCAO. Additionally, another thirty-five rats were employed for the time point. 
Results: TTC staining results demonstrated that AB4 significantly reduced cerebral infarct volume. Histopathological analysis of brain tissues revealed that AB4 mitigated neuronal damage. In the MCAO model, GRP78 expression progressively increased with reperfusion time and peaked at 24 hr. AB4 treatment decreased mRNA levels of key ERS markers, including GRP78, ATF6, IRE1α, and PERK. Additionally, AB4 reduced protein levels of GRP78, p-PERK, PERK, ATF6, and p-IRE1α, further indicating its role in attenuating ERS. TUNEL results demonstrated that AB4 significantly reduced neuronal apoptosis.
Conclusion: AB4 may serve as a potential therapeutic agent for CIRI, potentially exerting neuroprotective effects through inhibiting ERS-mediated apoptosis.

Keywords

Main Subjects

References

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Iranian Journal of Basic Medical Sciences
Volume 28, Issue 9
September 2025
Pages 1261-1267

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